Gusella, MacDonald, and their colleagues in the field of HD research have accomplished much in their careers. As mentioned earlier, Gusella mapped the Huntington gene to chromosome 4 in 1983. Dr. Gillian Bates of King’s College, London, cloned the tip of the chromosome, where the Huntington gene is located, and with Gusella and MacDonald, made a road map that pointed to the location of the gene. From there, researcher Christine Ambrose narrowed down the search for the gene to the two most promising segments of the tip, IT15 and IT16 (IT is lab lingo for “Interesting Transcript”). She discovered that these ITs were actually one gene, the Huntington gene. (Several neighboring ITs are now known to be inherited together with this gene.) Then, with her colleague Mabel Duyao, Ambrose made an assay that found that excess CAG repeats on the HD allele of the Huntington gene cause HD.
MacDonald got involved in the research effort in 1985, discovering new pieces of DNA on chromosome 4. In 1987, enough pieces of the chromosome were cloned to show various gene recombination events. Recombination events occur when genes lying farther apart on the same chromosome are often not inherited together due to the transfer of segments of DNA between homologous chromosomes during meiosis, the reproductive process by which sperm and egg cells are made. A haplotype study (a study describing the genetic makeup of an individual with respect to a specific pair of alleles or genes) was published in 1992. The objective of the study was to find out if the chromosomes on which the Huntington gene resides looked similar at a particular region in different people who had HD (in other words, the researchers wanted to know if the same mutation causes HD in everyone who has it). Through linkage studies (for more information, please click here), the researchers found that there was more than one mutation in ancestral populations (the predecessors of various groups of people who suffer from HD today). Interestingly, they also found the same mutation at the same spot in chromosome 4 in unrelated people with HD, so the same type of mutation in the same gene causes the disease in all people.
Last Modified: 05/22/2009
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